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Robert Sweet, MD

  • UPMC Professor of Psychiatric Neuroscience and Professor of Neurology
  • Director, Clinical Core, Alzheimer Disease Research Center
  • Director, T32, Training for Transformative Discovery in Psychiatry

    Education & Training

  • Medical School – University of Maryland - MD
Research Grants

NIH Grants:  R01, T32, P50

Research Summary

My research program is focused on identifying the genetic factors and the expressed brain phenotypes associated with the manifestation of psychotic symptoms. Psychotic symptoms are distressing, associated with cognitive and functional impairments, and poorly addressed by current treatments. My research consists of several studies testing the global hypothesis that there are genetic variations and brain alterations which lead to the expression of psychosis in conjunction with factors affecting neurodevelopment (leading to schizophrenia) or with factors leading to neurodegenerative processes (resulting in psychosis in Alzheimer disease). My approach is translational. The clinical component of my research program focuses on ascertainment and behavioral characterization of Alzheimer disease subjects with psychosis for large-scale genomic analysis using case-control and family-based designs. These studies have preliminarily identified several loci associated with psychosis risk in Alzheimer Disease. My lab studies are conducted in postmortem brain tissue from subjects with schizophrenia and Alzheimer disease. We are examining how the proteins coded by these loci, and other proteins which mediate structural plasticity at cerebral cortex synapses, are altered in disease. Mouse and in vitro models of neurodevelopment and neurodegeneration are then used to test hypothesized mechanisms.

Representative Publications
  1. Krivinko JM, Erickson SL, Ding Y, Sun Z, Penzes P, MacDonald ML, Yates NA, Ikonomovic MD, Lopez OL, Sweet RA, Kofler J. Synaptic Proteome Compensation and Resilience to Psychosis in Alzheimer's Disease. Am J Psychiatry. 2018 Oct 1;175(10):999-1009. doi: 10.1176/appi.ajp.2018.17080858. Epub 2018 Jul 19. PubMed PMID: 30021459; PubMed Central PMCID: PMC6167138.
  2. Russell TA, Grubisha MJ, Remmers CL, Kang SK, Forrest MP, Smith KR, Kopeikina KJ, Gao R, Sweet RA, Penzes P. A Schizophrenia-Linked KALRN Coding Variant Alters Neuron Morphology, Protein Function, and Transcript Stability. Biol Psychiatry. 2018 Mar 15;83(6):499-508. doi: 10.1016/j.biopsych.2017.10.024. Epub 2017 Nov 7. PubMed PMID: 29241584; PubMed Central PMCID: PMC5809265.
  3. DeMichele-Sweet MAA, Weamer EA, Klei L, Vrana DT, Hollingshead DJ, Seltman HJ, Sims R, Foroud T, Hernandez I, Moreno-Grau S, Tárraga L, Boada M, Ruiz A, Williams J, Mayeux R, Lopez OL, Sibille EL, Kamboh MI, Devlin B, Sweet RA. Genetic risk for schizophrenia and psychosis in Alzheimer disease. Mol Psychiatry. 2018 Apr;23(4):963-972. doi: 10.1038/mp.2017.81. Epub 2017 May 2. PubMed PMID: 28461698; PubMed Central PMCID: PMC5668212.
  4. MacDonald ML, Alhassan J, Newman JT, Richard M, Gu H, Kelly RM, Sampson AR, Fish KN, Penzes P, Wills ZP, Lewis DA, Sweet RA. Selective Loss of Smaller Spines in Schizophrenia. Am J Psychiatry. 2017 Jun 1;174(6):586-594. doi: 10.1176/appi.ajp.2017.16070814. Epub 2017 Mar 31. PubMed PMID: 28359200; PubMed Central PMCID: PMC5800878.
  5. Krivinko JM, Erickson SL, Abrahamson EE, Wills ZP, Ikonomovic MD, Penzes P, Sweet RA. Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice. Neurobiol Aging. 2017 Jun;54:59-70. doi: 10.1016/j.neurobiolaging.2017.02.006. Epub 2017 Feb 16. PubMed PMID: 28319837; PubMed Central PMCID: PMC5502748.
  6. Javitt DC, Sweet RA. Auditory dysfunction in schizophrenia: integrating clinical and basic features. Nat Rev Neurosci. 2015 Sep;16(9):535-50. doi: 10.1038/nrn4002. Review. PubMed PMID: 26289573; PubMed Central PMCID: PMC4692466.